The simian sarcoma virus transforming gene, v-sis, encodes a protein closely related to PDGF-2, a major component of platelet-derived growth factor (PDGF). Nucleotide sequence analysis has revealed that the human c-sis proto-oncogene, the normal homolog of v-sis, is the structural gene for PDGF polypeptide chain-2. The trancriptional product of the PDGF-2 gene is a 4.2-kb mRNA detected in certain human tumor cell lines as well as in normal human placenta and endothelial cells. To study the structure and function of this oncogene we constructed a cDNA library from normal human placental mRNA. We have isolated five cDNA clones representing the PDGF-2 transcript and the complete nucleotide sequence of one clone, pSD1, 2.6 kb in length, has been determined. Our data revealed a noncoding sequence of 1625 bp at the 3' end of the mRNA of which 1597 bp were contained within a single exon in genomic DNA. In spite of the presence of long 3' noncoding sequences, the c-sis transcript did not contain the highly conserved polyadenylation signal, AATAAA. Instead, this signal was observed 18 bp downstream of the site of polyadenylation in genomic DNA. The PDGF-2 coding sequence consisted of 723 bp located immediately upstream of the 3' non-coding stretch. We detected two upstream TGA codons, both of which were in phase with the initiator ATG codon. These and other findings establish that the 2.6-kb cDNA clones contain the entire coding sequence of the normal PDGF-2 precursor.